Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Trevisoli, Pablo Gil Mortol
Orientador(a): Borra, Ricardo Carneiro lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de São Carlos
Câmpus São Carlos
Programa de Pós-Graduação: Programa de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEv
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Área do conhecimento CNPq:
Link de acesso: https://repositorio.ufscar.br/handle/ufscar/10354
Resumo: Despite recent advances in cancer prevention and treatment, bladder urothelial carcinoma continues to be one of the most common types of malignant neoplasms in the world, with a 20% mortality rate. The cells and molecules of the immune system are fundamental components of the tumor microenvironment. Probably the fact that the neoplastic cell shares antigens with normal cells, have high growth rate and suffer edition, contributes to its resistance to the antitumor immune response. Even with these obstacles, the immune response remains one of the best bets in the malignant neoplasms treatment. In the past, homeostatic cell death, which often occurs through apoptosis, was irrelevant to the antitumor immune response since it was unable to stimulate the immune system. However, in recent years, it has been observed that certain types of apoptosis were able to induce immune response against dead cell antigens, particularly when they were derived from malignant neoplasms. This type of phenomenon was called immunogenic cell death (ICD). Despite advances in the discovery of the mechanisms involved in cell death associated with various tumor lines, no work to date has evaluated its efficacy in the model of bladder cancer induced by chemotherapeutics commonly used in the treatment of this disease.Therefore, the aim of the present study was to evaluate the action of cisplatin, mitoxantrone, daunorubicin, doxorubicin and epirubicin on the viability of MB49 lineage cellsand to identify the best dose with apoptotic activity of cisplatin, mitoxantrone, daunorubicin and doxorubicin. The results showed that chemotherapeutics agents, in their pharmaceutical formulation, performed well against MB49 cells in vitro. Cisplatin and mitoxantrone proved to be efficient in producing apoptosis, but only in vivo tests could confirm their immunogenic effect on these cells. In addition, this work showed that the effects of viability may be quite divergent depending on the dose and time evaluated and the need for a follow-up of viability after treatment withdrawal. In addition, this work showed that the effects of viability might be quite divergent depending on the dose and time evaluated and the need to observe viability after treatment withdrawal. It is concluded that the drug formulations of daunorubicin, epirubicin, doxorubicin and mitoxantrone produced varying degrees of apoptotic death in vitro, depending on exposure time and drug concentration.
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spelling Trevisoli, Pablo Gil MortolBorra, Ricardo Carneirohttp://lattes.cnpq.br/5655362515357840http://lattes.cnpq.br/25450133239543272018-08-13T18:31:32Z2018-08-13T18:31:32Z2018-03-29TREVISOLI, Pablo Gil Mortol. Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino. 2018. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10354.https://repositorio.ufscar.br/handle/ufscar/10354Despite recent advances in cancer prevention and treatment, bladder urothelial carcinoma continues to be one of the most common types of malignant neoplasms in the world, with a 20% mortality rate. The cells and molecules of the immune system are fundamental components of the tumor microenvironment. Probably the fact that the neoplastic cell shares antigens with normal cells, have high growth rate and suffer edition, contributes to its resistance to the antitumor immune response. Even with these obstacles, the immune response remains one of the best bets in the malignant neoplasms treatment. In the past, homeostatic cell death, which often occurs through apoptosis, was irrelevant to the antitumor immune response since it was unable to stimulate the immune system. However, in recent years, it has been observed that certain types of apoptosis were able to induce immune response against dead cell antigens, particularly when they were derived from malignant neoplasms. This type of phenomenon was called immunogenic cell death (ICD). Despite advances in the discovery of the mechanisms involved in cell death associated with various tumor lines, no work to date has evaluated its efficacy in the model of bladder cancer induced by chemotherapeutics commonly used in the treatment of this disease.Therefore, the aim of the present study was to evaluate the action of cisplatin, mitoxantrone, daunorubicin, doxorubicin and epirubicin on the viability of MB49 lineage cellsand to identify the best dose with apoptotic activity of cisplatin, mitoxantrone, daunorubicin and doxorubicin. The results showed that chemotherapeutics agents, in their pharmaceutical formulation, performed well against MB49 cells in vitro. Cisplatin and mitoxantrone proved to be efficient in producing apoptosis, but only in vivo tests could confirm their immunogenic effect on these cells. In addition, this work showed that the effects of viability may be quite divergent depending on the dose and time evaluated and the need for a follow-up of viability after treatment withdrawal. In addition, this work showed that the effects of viability might be quite divergent depending on the dose and time evaluated and the need to observe viability after treatment withdrawal. It is concluded that the drug formulations of daunorubicin, epirubicin, doxorubicin and mitoxantrone produced varying degrees of apoptotic death in vitro, depending on exposure time and drug concentration.Apesar dos recentes avanços nas áreas de prevenção e tratamento do câncer, o carcinoma urotelial de bexiga continua sendo um dos tipos mais comuns de neoplasias malignas no mundo, com índices de mortalidade de 20% dos casos. As células e moléculas do sistema imunológico são componentes fundamentais do microambiente tumoral. Provavelmente o fato de a célula neoplásica compartilhar antígenos com as células normais, de possuir alta taxa de crescimento e sofrer edição contribuem para a sua resistência em relação à resposta imunológica antitumoral. Mesmo com estes contratempos, a resposta imunológica continua sendo uma das melhores apostas no tratamento das neoplasias malignas. No passado, a morte celular homeostática, que muitas vezes ocorre por meio de apoptose, foi irrelevante para a resposta imune antitumoral uma vez que era incapaz de estimular o sistema imunológico. Porém, nos últimos anos, foi observado que certos tipos de apoptoses eram capazes de induzir resposta imune contra antígenos de células mortas, em particular quando elas eram derivadas de neoplasias malignas. Este tipo de fenômeno foi denominado de morte celular imunogênica (ICD). Apesar dos avanços na descoberta dos mecanismos envolvidos na morte celular associado às várias linhagens tumorais, nenhum trabalho até o presente momento avaliou sua eficácia em modelo de câncer de bexiga induzida pelos quimioterápicos comumente utilizados no tratamento dessa doença. Sendo assim, o presente trabalho procurou avaliar a ação dos quimioterápicos cisplatina, mitoxantrona, daunorrubicina, doxorrubicina e epirrubicina na viabilidade das células de linhagem MB49 e identificando a melhor dose com atividade apoptóticada cisplatina, mitoxantrona, daunorrubicina e doxorrubicina. Os resultados mostraram que os quimioterápicos em sua formulação farmacêutica apresentaram um bom desempenho contra as células MB49 in vitro e a cisplatina e a mitoxantrona mostraram-se eficientes em produzir apoptose, porém somente os testes in vivo poderão confirmar seu efeito imunogênico sobre essas células. Além disso, este trabalho mostrou que os efeitos da viabilidade podem ser bastante divergentes dependendo da dose e do tempo avaliados e a necessidade de um acompanhamento da viabilidade após a remoção dos tratamentos. Deste modo, conclui-se que as formulações medicamentosas da daunorrubicina, epirrubicina, doxorrubicina e da mitoxantrona produziram graus variados de morte apoptótica in vitro, dependente do tempo de exposição e da concentração dos medicamentos.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEvUFSCarCâncer de BexigaApoptoseCisplatinaMitoxantronaDaunorrubicinaDoxorrubicinaEpirrubicinaCIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULARCIENCIAS BIOLOGICAS::IMUNOLOGIACIENCIAS DA SAUDEComparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murinoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisOnlineinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTrevisoli PGM 2018 v final .pdfTrevisoli PGM 2018 v final .pdfapplication/pdf1282184https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/10354/1/Trevisoli%20PGM%202018%20v%20final%20.pdf8b7ef6c772f9646bb72b0bf5a82060f9MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/10354/4/license.txtae0398b6f8b235e40ad82cba6c50031dMD54TEXTTrevisoli PGM 2018 v final .pdf.txtTrevisoli PGM 2018 v final .pdf.txtExtracted texttext/plain110819https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/10354/5/Trevisoli%20PGM%202018%20v%20final%20.pdf.txt31000d6072c9ee267d2f87404dafffe0MD55THUMBNAILTrevisoli PGM 2018 v final .pdf.jpgTrevisoli PGM 2018 v final .pdf.jpgIM Thumbnailimage/jpeg6497https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/10354/6/Trevisoli%20PGM%202018%20v%20final%20.pdf.jpge354d09e30586216bb18bf4ac4732552MD56ufscar/103542019-09-11 03:19:57.427oai:repositorio.ufscar.br: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Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-05-25T12:56:18.998233Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino
title Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino
spellingShingle Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino
Trevisoli, Pablo Gil Mortol
Câncer de Bexiga
Apoptose
Cisplatina
Mitoxantrona
Daunorrubicina
Doxorrubicina
Epirrubicina
CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR
CIENCIAS BIOLOGICAS::IMUNOLOGIA
CIENCIAS DA SAUDE
title_short Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino
title_full Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino
title_fullStr Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino
title_full_unstemmed Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino
title_sort Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino
author Trevisoli, Pablo Gil Mortol
author_facet Trevisoli, Pablo Gil Mortol
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/2545013323954327
dc.contributor.author.fl_str_mv Trevisoli, Pablo Gil Mortol
dc.contributor.advisor1.fl_str_mv Borra, Ricardo Carneiro
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/5655362515357840
contributor_str_mv Borra, Ricardo Carneiro
dc.subject.por.fl_str_mv Câncer de Bexiga
Apoptose
Cisplatina
Mitoxantrona
Daunorrubicina
Doxorrubicina
Epirrubicina
topic Câncer de Bexiga
Apoptose
Cisplatina
Mitoxantrona
Daunorrubicina
Doxorrubicina
Epirrubicina
CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR
CIENCIAS BIOLOGICAS::IMUNOLOGIA
CIENCIAS DA SAUDE
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR
CIENCIAS BIOLOGICAS::IMUNOLOGIA
CIENCIAS DA SAUDE
description Despite recent advances in cancer prevention and treatment, bladder urothelial carcinoma continues to be one of the most common types of malignant neoplasms in the world, with a 20% mortality rate. The cells and molecules of the immune system are fundamental components of the tumor microenvironment. Probably the fact that the neoplastic cell shares antigens with normal cells, have high growth rate and suffer edition, contributes to its resistance to the antitumor immune response. Even with these obstacles, the immune response remains one of the best bets in the malignant neoplasms treatment. In the past, homeostatic cell death, which often occurs through apoptosis, was irrelevant to the antitumor immune response since it was unable to stimulate the immune system. However, in recent years, it has been observed that certain types of apoptosis were able to induce immune response against dead cell antigens, particularly when they were derived from malignant neoplasms. This type of phenomenon was called immunogenic cell death (ICD). Despite advances in the discovery of the mechanisms involved in cell death associated with various tumor lines, no work to date has evaluated its efficacy in the model of bladder cancer induced by chemotherapeutics commonly used in the treatment of this disease.Therefore, the aim of the present study was to evaluate the action of cisplatin, mitoxantrone, daunorubicin, doxorubicin and epirubicin on the viability of MB49 lineage cellsand to identify the best dose with apoptotic activity of cisplatin, mitoxantrone, daunorubicin and doxorubicin. The results showed that chemotherapeutics agents, in their pharmaceutical formulation, performed well against MB49 cells in vitro. Cisplatin and mitoxantrone proved to be efficient in producing apoptosis, but only in vivo tests could confirm their immunogenic effect on these cells. In addition, this work showed that the effects of viability may be quite divergent depending on the dose and time evaluated and the need for a follow-up of viability after treatment withdrawal. In addition, this work showed that the effects of viability might be quite divergent depending on the dose and time evaluated and the need to observe viability after treatment withdrawal. It is concluded that the drug formulations of daunorubicin, epirubicin, doxorubicin and mitoxantrone produced varying degrees of apoptotic death in vitro, depending on exposure time and drug concentration.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-08-13T18:31:32Z
dc.date.available.fl_str_mv 2018-08-13T18:31:32Z
dc.date.issued.fl_str_mv 2018-03-29
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv TREVISOLI, Pablo Gil Mortol. Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino. 2018. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10354.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/10354
identifier_str_mv TREVISOLI, Pablo Gil Mortol. Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino. 2018. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10354.
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Câmpus São Carlos
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dc.publisher.initials.fl_str_mv UFSCar
publisher.none.fl_str_mv Universidade Federal de São Carlos
Câmpus São Carlos
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